text: As far back as 1966, the ETH group had started to explore, once again in a model system, an alternative strategy of corrin synthesis in which the corrin ring would be closed between rings A and D. The project was inspired by the conceivable existence of a thus far unknown bond reorganization process. This  if existing  would make possible the construction of cobyric acid from one single starting material. Importantly, the hypothetical process, being interpreted as implying two sequential rearrangements, was recognized to be formally covered by the new reactivity classifications of sigmatropic rearrangements and electrocyclizations propounded by Woodward and Hoffmann in the context of their orbital symmetry rules!
  By May 1968, the ETH group had demonstrated in a model study that the envisaged process, a photochemical A/D-seco-corrinate→corrinate cycloisomerization, does in fact exist. This process was first found to proceed with the Pd complex, but not at all with corresponding Ni(II)- or cobalt(III)-A/D-seco-corrinate complexes. It also went smoothly in complexes of metal ions such as zinc and other photochemically inert and loosely bound metal ions. These, after ring closure, could easily be replaced by cobalt. These discoveries opened the door to what eventually became the photochemical A/D approach of cobyric acid synthesis.
  Starting in fall of 1969 with the B-C-component of the A/B approach and a ring-D precursor prepared from the enantiomer of the starting material leading to the ring-B precursor, it took PhD student Walter Fuhrer less than one and a half years to translate the photochemical model corrin synthesis into a synthesis of dicyano-cobalt(III)-5,15-bisnor-a,b,d,e,g-pentamethyl-cobyrinate-c-N,N-dimethylamide-f-nitrile 2 (fig. 4), the common corrinoid intermediate on the way to cobyric acid. At Harvard, the very same intermediate 2 was obtained around the same time by coupling the ring-D differentiated Harvard A-D-component (available in spring 1971) with the ETH B-C-component, applying the condensation methods developed earlier using the undifferentiated A-D-component.
  Thus, in spring 1971, two different routes to a common corrinoid intermediate 2 (fig. 4) along the way to cobyric acid had become available, one requiring 62 chemical steps (Harvard/ETH A/B approach), the other 42 (ETH A/D approach). In both approaches, the four peripheral rings derived from enantiopure precursors possessing the correct sense of chiral, thereby circumventing major stereochemical problems in the buildup of the ligand system. In the construction of the A/D-junction by the A/D-secocorrin→corrin cycloisomerization, formation of two A/D-diastereomers had to be expected. Using cadmium(II) as the coordinating metal ion led to a very high diastereoselectivity in favor of the natural A/D--isomer.
  Once the corrin structure was formed by either approach, the three C-H-chirogenic centers at the periphery adjacent to the chromophore system turned out to be prone to epimerizations with exceptional ease. This required a separation of diastereomers after most of the chemical steps in this advanced stage of the syntheses. It was fortunate indeed that, just around that time, the technique of high pressure liquid chromatography (HPLC) had been developed in analytical chemistry. HPLC became an indispensable tool in both laboratories; its use in the B project, pioneered by Jakob Schreiber at ETH, was the earliest application of the technique in natural product synthesis.